Patients with cancer of the oral cavity usually present with advanced stage disease. Treatment is more disfiguring and debilitating, more expensive, and less successful for these patients compared to those with earlier stage disease. Early detection of neoplastic changes in the oral cavity may be our best method to improve patient quality of life and survival rates. Unfortunately, there is no satisfactory mechanism at present to adequately screen and detect premalignant changes and early lesions in the oral cavity. Optical spectroscopy can detect changes in tissue architecture and biochemical composition by scanning the tissue surface with a small, flexible, fiber optic probe. This has been used to discriminate between normal and malignant tissues in various sites, including the cervix and colon. Preliminary data suggests that optical spectroscopy may be useful for detecting dysplastic and neoplastic oral cavity mucosa. The objective of this developmental project is to develop a new, noninvasive method of diagnosing dysplasia and neoplasia in oral cavity mucosa using fluorescence and reflectance spectroscopy. We have established a team of clinicians, scientists and engineers to accomplish this objective through the following specific aims: 1) To measure fluorescence and reflectance spectra of normal and neoplastic oral mucosa in normal volunteers and oral cancer patients; 2) To compare spectroscopic data to clinical diagnostic criteria and standard histologic parameters, to develop and evaluate the accuracy of diagnostic algorithms for automated recognition of oral cavity neoplasia; and 3) To investigate the mechanisms of fluorescence and reflectance changes during malignant progression in oral neoplasia by correlating the morphologic and molecular tissue composition with spectroscopic findings. Using a small, fiberoptic probe, we will obtain fluorescent and reflectant spectroscopic readings from 100 normal volunteers and 100 patients with oral cavity lesions. The patient readings will be correlated with clinical and histologic parameters. Ultimately, our goal is to develop a method to provide diagnostic information in near real time that is both sensitive and specific. This non-invasive system could be employed in dental offices and cancer prevention clinics to improve the detection and diagnosis of early oral cancer.